Parkinson's disease (PD) is set apart from other neurodegenerative diseases by our knowledge of the key biochemical defect. Dopamine replacement therapy is effective in treating the major symptoms of the illness. However, despite the availability of symptomatic therapies, patients experience a functional decline as a result of the progressive nature of the illness. A major unmet need in the treatment of PD is the identification of therapies that slow the rate of progression of neuronal degeneration. Proper investigation of therapies with neuroprotective potential requires an enormous amount of resources and the collaborative effort of multiple centers to evaluate for disease modifying effects over long durations. In addition, the development of biomarkers to reliably monitor disease progression is instrumental. The goal of this proposal is to demonstrate the expertise and experience of the research team at the Institute for Neurodegenerative Disorders (IND) in performing clinical research in PD. The investigators at IND have jointly conducted over 45 clinical trials. In the past five years we have successfully recruited and enrolled about 210 research participants (3.5/month) in PD trials with an average retention rate of 87%. Our success in recruitment stems from our relationship with advocacy groups, experience in advertising, and providing education to other health care providers about current research questions relevant to PD. In addition, IND has played a prominent role in the development of dopamine transporter imaging using, B-CIT and SPECT in over 15 multi-center trials. The experienced research staff at IND is attentive to regulatory issues, safety monitoring and we are committed to closely adhere to the study protocols. As active members of the PD research community we propose to collaborate with a central Coordination Center, a Statistical Center and other clinical centers to provide input and recommendations toward the development of trials for the evaluation of potentially neuroprotective therapies. As a clinical center, we will recruit and comprehensively evaluate 12 participants in;the first year for the pilot studies and 72 participants in the following three years for the large simple trial that is under development. As an imaging center, we propose to play a key role in the development of studies to include subsets of participants in these neuroprotective trials.